DEPARTMENT OF HEALTH AND HUMAN SERVICESCenters for Disease Control and PreventionNational Institute for Occupational Safety and Health

NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2014

DEPARTMENT OF HEALTH AND HUMAN SERVICESCenters for Disease Control and Prevention

National Institute for Occupational Safety and Health

NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2014

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Suggested CitationNIOSH [2014]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2014. By Connor TH, MacKenzie BA, DeBord DG, Trout DB, O’Callaghan JP.. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupa-tional Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150).

DHHS (NIOSH) Publication Number 2014-138 (Supersedes 2012-150)

September 2014

Safer • Healthier • PeopleTM

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Preamble:. The National Institute for Occupational Safety and Health (NIOSH) Alert: Preventing Occu-pational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings was published in September 2004, http://www.cdc.gov/niosh/docs/2004-165/. In Appendix A of the Alert, NIOSH iden-tified a sample list of major hazardous drugs. The list was compiled from information provided by four institutions that had generated lists of hazardous drugs for their respective institutions, as well as a list from the Pharmaceutical Research and Manufacturers of America (PhRMA). The 2004 list was updated in 2010 and 2012. The current update (2014) adds 27 drugs and includes a review of the 2004 list and the consequent removal of 12 drugs that did not meet the NIOSH criteria for hazardous drugs. In addition, a new format has been developed for the list of hazardous drugs, as described below. The review process for the addition of the new listings is described in the Federal Register: http://www.cdc.gov/niosh/docket/review/docket233/pdf/CDC-2013-0007.pdf.

General Approach to Handling Hazardous Drugs

In the Alert (NIOSH 2004) and updates to the haz-ardous drug list (NIOSH 2012), NIOSH has recom-mended standard precautions or universal precau-tions be taken in handling hazardous drugs. Given the addition of many non-antineoplastic drugs and drugs in tablet and/or capsule form to the list, no single approach can cover the diverse potential occupational exposures to the drugs. The current NIOSH approach involves three groups of drugs:

� Group 1: Antineoplastic drugs (AHFS Classifi-cation 10:00) [ASHP/AHFS DI 2013]. Note that many of these drugs may also pose a reproduc-tive risk for susceptible populations (Table 1).

� Group 2: Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a haz-ardous drug. Note that some of these drugs may also pose a reproductive risk for susceptible populations (Table 2).

� Group 3: Drugs that primarily pose a reproduc-tive risk to men and women who are actively trying to conceive and women who are pregnant or breast feeding, because some of these drugs may be present in breast milk (Table 3).

The majority of the reproductive risks associat-ed with the drugs listed in Table 3 are focused on

women, but some can apply to men only (such as re-duced fertility or sperm count) or to both men and women. Although all hazardous drugs should be handled accordingly, especially if they must be pre-pared aseptically, some populations of workers may not be at serious risk from handling drugs in Group 3. These include workers who are excluded from the susceptible populations for specific reasons such as age or infertility. In addition, drugs for which the manufacturer includes safe-handling guidance in the package insert are indicated. NIOSH carries out a hazard identification on each drug on the basis of the NIOSH criteria for a hazardous drug. No attempt has been made to perform risk assess-ments on each drug or to propose exposure limits. NIOSH has provided guidance for personal protec-tive equipment and ventilated engineering controls for some of the various scenarios in which a drug may be handled in health care settings (Table 5). This guidance cannot cover all possible situations but provides general recommendations for the ma-jor handling events typically seen in health care.

Defining Hazardous Drugs

Hazardous drugs include those used for cancer che-motherapy, antiviral drugs, hormones, some bioen-gineered drugs, and other miscellaneous drugs. The definition of hazardous drugs used in the Alert is based on a definition originally developed in 1990 by the American Society of Hospital Pharmacists

Appendix A · Drugs Considered Hazardous

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[ASHP 1990], currently known as the American Society of Health-System Pharmacists. Thus, the definition may not accurately reflect the potential toxicity criteria associated with some of the new-er-generation pharmaceuticals entering the health care setting. For example, bioengineered drugs tar-get specific sites in the body, and although they may or may not pose a risk to health care workers, some may pose a risk to patients.

NIOSH and other organizations are still gathering data on the potential toxicity and health effects relat-ed to highly potent drugs and bioengineered drugs. Therefore, when working with any hazardous drug, health care workers should follow the approaches described in Table 5, along with any recommen-dations included in the manufacturer’s Safety Data Sheet (SDS).

ASHP Definition of Hazardous Drugs

ASHP defines hazardous drugs in its 1990 revision of the Technical Assistance Bulletin on Handling Hazardous Drugs [ASHP 1990]. The bulletin gives criteria for identifying potentially hazardous drugs that should be handled in accordance with an es-tablished safety program [McDiarmid et al. 1991; Arrington and McDiarmid 1993; ASHP 2006; Mas-soomi et al. 2008; Eisenberg 2009; ONS 2011]. The criteria are prioritized to reflect the hierarchy of potential toxicity described below. Since the haz-ardous drugs covered by the Alert were designed as therapeutic agents for humans, human toxicity pro-files should be considered superior to any data from animal models or in vitro systems. Additional guid-ance for defining hazardous drugs is available in the following sources: carcinogenicity [61 Fed Regist 17960–18011 (1996b); IARC 2014], teratogenicity [56 Fed Regist 63798–63826 (1991)], developmen-tal toxicity [56 Fed Regist 63798–63826 (1991)], and reproductive toxicity [61 Fed Regist 56274–56322 (1996a)]. Physical characteristics of the agents (such as liquid versus solid or water versus lipid solubility) also need to be considered in determining the po-tential for occupational exposure.

NIOSH Revision of ASHP Definition

The 1990 ASHP definition of hazardous drugs* was revised by the NIOSH Working Group on Hazard-ous Drugs for the Alert. Drugs considered hazard-ous include those that exhibit one or more of the following six characteristics in humans or animals:

� Carcinogenicity � Teratogenicity or other developmental

toxicity†

� Reproductive toxicity†

� Organ toxicity at low doses†

� Genotoxicity‡

� Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria

*ASHP [1990] definition of hazardous drugs

1. Genotoxicity (i.e., mutagenicity and clastogenicity in short-term test systems)

2. Carcinogenicity in animal models, in the patient popu-lation, or both, as reported by the International Agency for Research on Cancer (IARC)

3. Teratogenicity or fertility impairment in animal studies or in treated patients

4. Evidence of serious organ or other toxicity at low doses in animal models or treated patients.

†All drugs have toxic side effects, but some exhibit toxicity at low doses. The level of toxicity reflects a continuum from rel-atively nontoxic to production of toxic effects in patients at low doses (for example, a few milligrams or less). For exam-ple, a daily therapeutic dose of 10 mg/day or a dose of 1 mg/kg per day in laboratory animals that produces serious organ toxicity, developmental toxicity, or reproductive toxicity has been used by the pharmaceutical industry to develop occu-pational exposure limits (OELs) of less than 10 µg/m3 after applying appropriate uncertainty factors [Sargent and Kirk 1988; Naumann and Sargent 1997; Sargent et al. 2002]. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. Under all circumstances, an evaluation of all available data should be conducted to protect health care workers.

‡In evaluating mutagenicity for potentially hazardous drugs, re-sponses from multiple test systems are needed before precau-tions can be required for handling such agents. The EPA eval-uations include the type of cells affected and in vitro versus in vivo testing [51 Fed. Regist. 34006–34012 (1986)].

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Determining Whether a Drug is Hazardous

Many hazardous drugs used to treat cancer (for exam-ple, alkylating agents) bind to or damage DNA. Oth-er antineoplastic drugs, some antivirals, antibiotics, and bioengineered drugs interfere with cell growth or proliferation, or with DNA synthesis. In some cases, the nonselective actions of these drugs disrupt the growth and function of both healthy and diseased cells, resulting in toxic side effects for treated patients and their offspring. These nonselective actions can also cause adverse effects in health care workers who are inadvertently exposed to hazardous drugs.

Early concerns about occupational exposure to an-tineoplastic drugs first appeared in the 1970s. Al-though the antineoplastic drugs remain the principal focus of the Alert, other drugs may also be considered hazardous because they are potent (small quantities produce a physiological effect) or cause irreversible effects. As the use and number of these potent drugs increase, so do opportunities for hazardous expo-sures among health care workers. For example, an-tineoplastic drugs such as cyclophosphamide have immunosuppressant effects that proved beneficial for treating nonmalignant diseases such as rheuma-toid arthritis and multiple sclerosis [Baker et al. 1987; Moody et al. 1987; Chabner et al. 1996; Abel 2000]. The lack of proper training for handling antineoplas-tic drugs in other specialty areas may be an issue that needs to be addressed [Polovich and Giesker 2011; Menonna-Quinn et al. 2013].

This document presents criteria and sources of in-formation for determining whether a drug is haz-ardous. When a drug has been judged to be hazard-ous, the various precautions outlined in the Alert should be applied when handling that drug. Also included is a list of drugs that should be handled as hazardous. When applying the criteria for a hazard-ous drug as outlined above, NIOSH takes the fol-lowing approach.

� NIOSH takes into account the dose for animal testing, for reproductive and developmental tox-icity, and for carcinogenicity testing. If adverse effects are observed near, at, or below the max-imum recommended human dose (MRHD),

NIOSH considers it to be highly relevant. If dos-es producing an adverse effect are many times the MRHD, usually NIOSH does not consider them in its evaluation.

� In addition to dose, for carcinogenicity testing NIOSH looks for tumors in more than one species and sex. It looks for tumors in multiple organs and for tumors that are not rodent-specific. Any avail-able human data are considered significant.

� For effects of genotoxicity, NIOSH looks at in vivo testing over in vitro testing. However, ad-verse outcomes in several in vitro tests will be considered in its evaluation.

� For reproductive and developmental effects, NIOSH notes if there was maternal toxicity, in addition to the dose. Effects on the fetus in the absence of maternal toxicity are considered rele-vant. Drugs with an FDA pregnancy category X rating are typically listed as hazardous. Drugs in Category D are often listed as hazardous, but it will depend on the individual drug. Any avail-able human data are considered significant.

� For organ toxicity, the low dose criterion in the definition (a daily therapeutic dose of 10 mg/day or a dose of 1 mg/kg per day in laboratory ani-mals) is used as a benchmark.

� Drugs with safe-handling guidelines from the manufacturer are automatically put on the list because the manufacturer has decided their properties warrant special handling.

In addition to using the list of hazardous drugs pre-sented here, each organization should create its own list of drugs considered to be hazardous. This doc-ument presents guidance for making such a facili-ty-specific list (see section entitled How to Generate Your Own List of Hazardous Drugs). Subsequently, newly purchased drugs should be evaluated against the organization’s hazardous drug criteria and add-ed to the list if they are deemed hazardous. Organi-zations have developed various approaches to iden-tifying and classifying hazardous drugs [Chaffee et al. 2010; Badry et al. 2013; Kaestli et al. 2013]. Al-though the classification schemes may differ some-what, the drugs listed as hazardous are quite similar.

Individual organizations may not have adequate re-sources for determining their own list of hazardous

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drugs. If so, the list of hazardous drugs in this docu-ment will help employers and workers to determine when precautions are needed. However, reliance on such a published list is a concern because it quickly becomes outdated as new drugs continually enter the market or listed drugs are removed when addi-tional information becomes available. NIOSH will update this list periodically, adding new drugs con-sidered to be hazardous and removing those that re-quire reclassification. This hazardous drug list will be posted on the NIOSH website at www.cdc.gov/niosh/topics/hazdrug/.

How to Generate Your Own List of Hazardous Drugs

The OSHA hazard communication standard [29 CFR 1910.1200] requires employers to develop a hazard communication program appropriate for their unique workplaces. An essential part of the program is the identification of all hazardous drugs a worker may encounter in the facility. Compliance with the OSHA hazard communication standard entails (1) evaluating whether these drugs meet one or more of the criteria for defining hazardous drugs and (2) posting a list of the hazardous drugs to en-sure worker safety. Institutions may wish to com-pare their lists to the listing in this document or on the NIOSH website.

It is not likely that every health care provider or fa-cility will use all drugs that have received U.S. Food and Drug Administration (FDA) approval, and the OSHA hazard communication standard does not mandate evaluation of every marketed drug. In-stead, compliance requires practice-specific assess-ments for drugs used at any one time by a facility. However, hazardous drug evaluation is a continual process. Local hazard communication programs should provide for assessment of new drugs as they enter the marketplace and, when appropriate, reas-sessment of their presence on hazardous drug lists as toxicological data become available to support re-categorization. Toxicological data are often in-complete or unavailable for investigational drugs. However, if the mechanism of action suggests that

there may be a concern, it is prudent to handle them as hazardous drugs until adequate information be-comes available to exclude them.

With the increased availability of oral antineoplastic and other hazardous drugs, additional precautions are required in order to prevent worker exposure to these formulations. Some drugs defined as hazardous may not pose a significant risk of direct occupational expo-sure because of their dosage formulation (for example, coated tablets or capsules—solid, intact medications that are administered to patients without modifying the formulation). However, they may pose a risk if the formulations are altered, such as by crushing tablets or making solutions from them outside a ventilated cabi-net [Simmons 2010; Goodin et al. 2011]. Uncoated tab-lets may present a risk of exposure from dust by skin contact and/or inhalation when the tablets are counted [Shahsavarani et al. 1993].

All hazardous drugs, regardless of the formulation, should be labeled as such to prevent improper han-dling. Tablet and capsule forms of hazardous drugs should not be placed in automated counting ma-chines, which subject them to stress and may intro-duce powdered contaminants into the work area. Counting and pouring of hazardous drugs should be done carefully, and clean equipment should be ded-icated for use with these drugs. Crushing tablets or opening capsules should be avoided and liquid for-mulations should be used whenever possible. During the compounding of hazardous drugs (e.g., crushing, dissolving, or preparing a solution or an ointment), workers should wear non-permeable gowns and double gloves (Table 5). Guidelines for the safe com-pounding, administration, and disposal of hazardous drugs have been developed by several organizations [NIOSH 2004; ASHP 2006; ONS 2011; USP 2014].

Where to Find Information Related to Drug Toxicity

Practice-specific lists of hazardous drugs (usually developed by pharmacy or nursing departments) should be comprehensive, including all hazardous medications routinely used or very likely to be used

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by a local practice. Here are some of the resources that employers can use to evaluate the hazard po-tential of a drug:

� Safety Data Sheets (SDSs, formally Material Safety Data Sheets)

� Product labeling approved by the U.S. FDA (drug package inserts)

� International Agency for Research on Cancer (IARC) http://www.iarc.fr

� Drugbank: http://www.drugbank.ca/ � DailyMed: http://dailymed.nlm.nih.gov/dai-

lymed/ � Special health warnings from drug manufac-

turers, FDA, and other professional groups and organizations

� Reports and case studies published in medical and other health care profession journals

� Evidence-based recommendations from other facilities that meet the criteria defining hazard-ous drugs

Identification of Hazardous Drugs

The following list (Tables 1–3) contains those drugs that NIOSH has reviewed according to the criteria in the NIOSH definition of a hazardous drug. The list was compiled from the following:

� the original list published in 2004 (NIOSH 2004), which was a compilation of five lists avail-able to NIOSH at the time (subsequently, the list was re-evaluated against the NIOSH criteria and several drugs were removed; Table 4a)

� the 2012 NIOSH update to the list � the NIOSH 2014 update to the list, for which 27

drugs were added (including five with manufac-turers’ safe-handling warnings) and one drug, tetracycline, was deleted on the basis of re-evalu-ation and feedback from stakeholders (Table 4b).

The OSHA hazard communication standard re-quires hazardous drugs to be handled with use of special precautions. The mandate applies not only to health care professionals who provide direct patient

care but also to others who support patient care by participating in product acquisition, storage, trans-portation, housekeeping, and waste disposal. Insti-tutions may want to adopt this list or compare theirs with the list on the NIOSH website.

CAUTION: Drugs purchased and used by a facility may have entered the marketplace after the list be-low was assembled. Therefore, this list may not be all-inclusive.

If you use a drug that is not included in the list of hazardous drugs, check the available literature to see whether the unlisted drug should be treated as hazardous. Check the SDS from the manufactur-er or the drug package insert. You may also check with other institutions that might be using the same drug. If any of the documents mention carcinoge-nicity, genotoxicity, teratogenicity (Section 13 in package insert), or reproductive or developmental toxicity (Section 8), or if the package insert contains safe-handling warnings (Section 16), use the pre-cautions stipulated in the Alert. If the drug meets one or more of the criteria for hazardous drugs in the NIOSH definition, handle it as hazardous.

The list of hazardous drugs will be updated period-ically on the website, hpp://www.cdc.gov/niosh/top-ics/hazdrug/.

This list supersedes both the 2004 list, http://www.cdc.gov/niosh/docs/2004-165/ and the 2012 list http://www.cdc.gov/niosh/docs/2012-150.

References

Abel EA [2000]. Immunosuppressant and cytotoxic drugs: unapproved uses or indications. Clin Derma-tol 18:95–101.

Arrington DM, McDiarmid MA [1993]. Comprehensive program for handling hazardous drugs. Am J Hosp Pharm 50:1170–1174.

ASHP (American Society of Hospital Pharmacists) [1990]. ASHP technical assistance bulletin on han-dling cytotoxic and hazardous drugs. Am J Hosp Pharm 47:1033–1049.

ASHP (American Society of Health-System Pharmacists) [2006]. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm 63:1172–1193.

ASHP/AHFS DI (American Hospital Formulary Service Drug Information) [2013]. AHFS drug information online updates, www.ahfsdruginformation.com.

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Baker GL, Kahl LE, Zee BC, Stolzer BL, Agarwal AK, Medsger TA Jr [1987]. Malignancy following treat-ment of rheumatoid arthritis with cyclophospha-mide. Long-term case-control follow-up study. Am J Med 83(1):1–9.

Badry N, Fabbro J, de Lemos ML [2013]. Hazards in determining whether a drug is hazardous. J Oncol Pharm Pract. doi: 10.1177/1078155213496675 (pub-lished online 20 August).

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Chabner BA, Allegra CJ, Curt GA, Calabresi P [1996]. Antineoplastic agents. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s the pharmacological ba-sis of therapeutics. 9th ed. New York: McGraw-Hill, pp. 1233–1287.

Chaffee BW, Armistead JA, Benjamin BE, Cotugno MC, Forrey RA, Hintzen BL, Pfeiffenberger T, Stevenson JG [2010]. Guidelines for the safe handling of haz-ardous drugs: consensus recommendations. Am J Health-Syst Pharm 67:1545–1546.

Eisenberg S [2009]. Safe handling and administration of antineoplastic chemotherapy. J Infus Nurs 32(1):23–32.

Goodin S, Griffith N, Chen B, Chuk K, Daouphars M, Doreau C, Patel RA, Schwartz R, Tames MJ, Terkola R, Vadnais B, Wright D, Meier K [2011]. Safe han-dling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract 7(1):7–8.

IARC [2014]. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Lyon, France: World Health Organization, International Agency for Research on Cancer. www. iarc.fr. Date accessed: March 2014.

Kaestli L-Z, Fonzo-Christe C, Bonfillon C, Desmueles J, Bonnabry P [2013]. Development of a standardized method to recommend protective measures to han-dle hazardous drugs in hospitals. Eur J Hosp Pharm 20:100–105.

Massoomi F, Neff B, Rick A, Denekas P [2008]. Imple-mentation of a safety program for handling hazard-ous drugs in a community hospital. Am J Heath-Sys Pharm 65:861–865.

McDiarmid MA, Gurley HT, Arrington D [1991]. Phar-maceuticals as hospital hazards: managing the risks. J Occup Med 33(2):155–158.

Menonna-Quinn D [2013]. Safe handling of chemother-apeutic agents in the treatment of nonmalignant dis-eases. J Infus Nurs 36(3):198–204.

Moody DJ, Kagan J, Liao D, Ellison GW, Myers LW [1987]. Administration of monthly-pulse cyclophos-phamide in multiple sclerosis patients. Effects of

long-term treatment on immunologic parameters. J Neuroimmunol 14(2):161–173.

Naumann BD, Sargent EV [1997]. Setting occupation-al exposure limits for pharmaceuticals. Occup Med: State of the Art Rev 12(1):67–80.

NIOSH [2004]. NIOSH alert: preventing occupation-al exposure to antineoplastic and other hazardous drugs in health care settings. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

NIOSH [2012]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2012-150 (September). http:// nioshdev.cdc.gov/niosh/docs/2012-150.

ONS (Oncology Nursing Society) [2011]. Safe handling of hazardous drugs. 2nd Ed. M. Polovich, ed. Pitts-burgh, PA: Oncology Nursing Society.

Polovich M, Giesker KE [2011]. Occupational hazardous drug exposure among non-oncology nurses. Medsurg Nurs 20(2):79–85,97.

Sargent EV, Kirk GD [1988]. Establishing airborne ex-posure control limits in the pharmaceutical industry. Am Ind Hyg Assoc J 49(6):309–313.

Sargent EV, Naumann BD, Dolan DG, Faria EC, Schul-man L [2002]. The importance of human data in the establishment of occupational exposure limits. Hum Ecol Risk Assess 8(4):805–822.

Shahsavarani S, Godefroid RJ, Harrison BR [1993]. Eval-uation of occupational exposure to tablet trituration dust [abstract]. ASHP Midyear Clinical Meeting. Document No. P-59(E).

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Acknowledgments

This document was written by Thomas H. Connor, PhD; Barbara A. MacKenzie, BS; D. Gayle DeBord, PhD; Douglas B. Trout, MD, MHS; and James P. O’Callaghan, PhD, all of NIOSH.

Seleen Collins provided editorial services. Ryan Dufour, Nicole Romero, and Vanessa Williams pro-vided graphic design and production services.

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NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014NIOSH performs a hazard identification on each of the drugs in the following tables. The actual risk to health care workers depends on what is done with the drugs—how they are manipulated, how often they are handled, and what type of engineering con-trols and personal protective equipment (PPE) are used (see Table 5). For example,

� Dispensing a single tablet to a patient poses little to no risk to the healthcare worker. A single pair of gloves would be adequate.

� Repeatedly counting, cutting, or crushing tab-lets may pose a higher risk of worker exposure and contamination to the workplace if proper precautions are not in place. If a containment

device such as a BSC (Class II biological safety cabinet) or CACI (compounding aseptic con-tainment isolator) is not available, then double gloves, a protective gown, respiratory protec-tion, and a disposable pad to protect the work surface should be used.

� Preparing a number of intravenous doses of an antineoplastic drug typically poses a higher po-tential risk to the worker. In addition to double gloving and a protective gown, an engineering control such as a BSC or CACI, possibly supple-mented with a CSTD (closed system drug trans-fer device), is required to protect the drug, envi-ronment, and health care worker.

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Table 1. Antineoplastic drugs including those with manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

abiraterone* 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

ado- trastuzumab emtansine

10:00 antineoplastic agents yes Conjugated monoclonal antibody; FDA Pregnancy Category D

DailyMed; DrugBank

altretamine 10:00 antineoplastic agents yes FDA Pregnancy category D DailyMed; DrugBank

amsacrine NA antineoplastic agents yes IARC Group 2B DrugBank

anastrozole 10:00 antineoplastic agents FDA Pregnancy category X DailyMed; DrugBank

arsenic trioxide 10:00 antineoplastic agents yes IARC Group 1 carcinogen**; FDA Pregnancy Category D

DailyMed; DrugBank

azacitidine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

bacillus calmette Guerin (BCG)***

80:12 vaccines yes See special handling requirements**; FDA Preg-nancy Category C

DailyMed

bendamustine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed;

bexarotene 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

The drugs in Table 1 meet one or more of the NIOSH criteria for a hazardous drug. These drugs represent an occupational hazard to health care workers and should always be handled with use of recommended engi-neering controls and personal protective equipment (PPE), regardless of their formulation (IV [intravenous], SC [subcutaneous], topical, tablet, or capsule). Unopened, intact tablets and capsules may not pose the same degree of occupational exposure risk as injectable drugs, which usually require extensive preparation. Cut-ting, crushing or otherwise manipulating tablets and capsules will increase the risk of exposure to workers. In addition to many of these drugs being cytotoxic, the majority are hazardous to males or females who are actively trying to conceive, women who are pregnant or may become pregnant, or women who are breast feed-ing, because they may be present in breast milk. Manufacturers’ safe-handling guidance (MSHG) is typically in Section 16 of the drug package insert. See Table 5 for safe-handling recommendations. AHFS = American Hospital Formulary Service; MHRD = maximum recommended human dose.*Drugs in red font were added in 2014.**International Agency for Research on Cancer (www.iarc.fr).***BCG, although classified as a vaccine, is used in the treatment of certain cancers. BCG should be prepared with aseptic techniques. To avoid cross-contamination, parenteral drugs should not be prepared in areas where BCG has been prepared. A separate area for the preparation of BCG suspension is recommended. All equipment, supplies, and receptacles in contact with BCG should be handled and disposed of as biohazardous. If preparation cannot be performed in a containment device, then respiratory protection, gloves, and a gown should be worn to avoid inhalation or contact with BCG organisms.

(continued)

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Drug AHFS classification MSHG Reason for listing Links

bicalutimide 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

bleomycin 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg-nancy Category D

DailyMed; DrugBank

bortezomib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

brentuximab vedotin

10:00 antineoplastic agents yes Conjugated monoclonal antibody; FDA Pregnancy Category D

DailyMed; DrugBank

busulfan 10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

cabazitaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

capecitabine 10:00 antineoplastic agents yes Metabolized to 5-fluoro-uracil; FDA Pregnancy Cate-gory D

DailyMed; DrugBank

carboplatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

carmustine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

chlorambucil 10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

cisplatin 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

cladribine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

clofarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

crizotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed

cyclophospha-mide

10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; Drugbank

cytarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

dacarbazine 10:00 antineoplastic agents yes FDA Pregnancy Category C DailyMed; Drugbank

dactinomycin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

dasatinib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

daunorubicin 10:00 antineoplastic agents yes IARC Group 2B, AKA dauno-mycin; FDA Pregnancy Cat-egory D

DailyMed; Drugbank

Table 1 (Contintued). Antineoplastic drugs including those with manufacturers’ safe handling guidance (MSHG)

(continued)

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Drug AHFS classification MSHG Reason for listing Links

decitabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

degarelix 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; Drugbank

docetaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

doxorubicin 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

epirubicin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

eribulin 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

erlotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

estramustine 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; Drugbank

etoposide 10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

everolimus 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

exemestane 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

floxuridine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

fludarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

fluorouracil 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

flutamide 10:00 antineoplastic agents Indicated only for men; FDA Pregnancy Category D

DailyMed; DrugBank

fulvestrant 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

gemcitabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

gemtuzumab ozogamicin

10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

goserelin 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; Drugbank

hydroxyurea 10:00 antineoplastic agents yes Special warning on handling bottles and capsulesFDA Pregnancy Category D

DailyMed; DrugBank

idarubicin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

ifosfamide 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

Table 1 (Contintued). Antineoplastic drugs including those with manufacturers’ safe handling guidance (MSHG)

(continued)

10 11

Table 1 (Contintued). Antineoplastic drugs including those with manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

imatinib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

irinotecan 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

ixabepilone 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

letrozole 10:00 antineoplastic agents FDA pregnancy Category X DailyMed; DrugBank

leuprolide 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; Drugbank

lomustine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

mechloreth-amine

10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

megestrol 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed; DrugBank

melphalan 10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

mercaptopurine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

methotrexate 10:00 antineoplastic agents yes FDA Pregnancy Category X DailyMed; DrugBank

mitomycin 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg-nancy Category D

DailyMed; DrugBank

mitotane 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

mitoxantrone 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg-nancy Category D

DailyMed; DrugBank

nelarabine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

nilotinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

omacetaxin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

oxaliplatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

paclitaxel 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

pazopanib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

pemetrexed 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

pentostatin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

pralatrexate 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

(continued)

12 13

Table 1 (Contintued). Antineoplastic drugs including those with manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

procarbazine 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

romidepsin 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed

sorafenib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

streptozocin 10:00 antineoplastic agents yes IARC Group 2B; FDA Preg-nancy Category D

DailyMed; DrugBank

sunitinib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

tamoxifen 10:00 antineoplastic agents IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

temozolomide 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

temsirolimus 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

teniposide 10:00 antineoplastic agents yes IARC Group 2A carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

thioguanine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

thiotepa 10:00 antineoplastic agents yes IARC Group 1 carcinogen; FDA Pregnancy Category D

DailyMed; DrugBank

topotecan 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

toremifene 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

trimetrexate 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

triptorelin 10:00 antineoplastic agents FDA Pregnancy Category X DailyMed

valrubicin 10:00 antineoplastic agents yes FDA Pregnancy Category C DailyMed; DrugBank

vandetanib 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vemurafenib 10:00 antineoplastic agents FDA Pregnancy Category D DailyMed; DrugBank

vinblastine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vincristine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

vinorelbine 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; DrugBank

vorinostat 10:00 antineoplastic agents yes FDA Pregnancy Category D DailyMed; Drugbank

12 13

Table 2. Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

abacavir* 8:18.08.20 nucleoside and reverse transcriptase inhibitors

FDA Pregnancy Category C;malignant tumors observed in male and female mice and rats; genotoxic in in vivo micronucleus test.

DailyMed; DrugBank

alefacept 84:92 skin and mucous membrane agents, miscel-laneous

Increased frequency of malignancies observed in treated patients; FDA Preg-nancy Category B

DailyMed; DrugBank

apomorphine 28:36.20.08 Nonergot- derivative dopamine receptor agonists

FDA Pregnancy Category C;genotoxic in several in vitro assays.

DailyMed; DrugBank

azathioprine 92:44 immunosuppressant agents

yes IARC Group 1 carcinogen**; FDA Pregnancy Category D***

DailyMed; DrugBank

carbamazepine 28:12:92 anticonvulsants, miscellaneous

Black Box warning for aplastic anemia; congenital malformations in offspring of mothers who took drug; rapid transplacental passage; FDA Pregnancy Category D

DailyMed; Drugbank

The drugs in Table 2 meet one or more of the NIOSH criteria for a hazardous drug. Unopened, intact tablets and capsules may not pose the same degree of occupational exposure risk as injectable drugs, which usually require extensive preparation. Cutting, crushing, or otherwise manipulating tablets and capsules will increase the risk of exposure to workers. Some of these drugs may represent an occupational hazard to males or females who are actively trying to conceive, women who are pregnant or may become pregnant, or women who are breast feeding, because they may be present in breast milk. Manufacturers’ safe-handling guidance (MSHG) is typically in Section 16 of the drug package insert. See Table 5 for safe-handling recommendations. AHFS = American Hospital Formulary Service; MHRD = maximum recommended human dose.*Drugs in red font were added in 2014.**International Agency for Research on Cancer, www.iarc.fr***Drugs in blue font meet one or more additional criteria for a hazardous drug and also pose a potential re-productive hazard.

(continued)

14 15

Table 2 (Contintued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

chloramphenicol 8:12:08 chloramphenicols IARC Group 2A carcinogen; FDA Pregnancy Category C

DailyMed; DrugBank

cidofovir 8:18:32 nucleoside and nucleotides

yes FDA Pregnancy Category C DailyMed; Drugbank

cyclosporine 92:44 immunosuppressive agents

IARC Group 1 carcinogen; FDA pregnancy Category C

DailyMed; Drugbank

deferiprone 64:00 Heavy metal antagonists

Genotoxic in vitro and in vivo; FDA Pregnancy Category D

DailyMed; DrugBank

dexrazoxane 92:56 protective agents yes FDA Pregnancy Category C;secondary malignancies observed in patients treated long term with Razoxane (a racemic mixture containing dexrazane); genotoxic in vitro and in vivo; in labo-ratory studies, testicular atrophy observed at or below the human dose

DailyMed; DrugBank

diethylstilbestrol NA IARC Group 1 carcinogen; FDA Pregnancy Category X

DrugBank

divalproex 28:12:92 anticonvulsants, miscellaneous

Black Box warning for tera-togenicity; FDA Pregnancy Category D; tumors seen in laboratory studies at doses below MRHD

DailyMed

entecavir 8:18:32 nucleosides and nucleotides

yes FDA Pregnancy Category C DailyMed; DrugBank

(continued)

14 15

Table 2 (Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

estradiol 68:16:04 estrogens Black Box warning for malig-nant neoplasms; increased risk of endometrial cancer, breast cancer, and ovarian cancer; in laboratory studies, increased frequency of carci-nomas of the breast, uterus, cervix, vagina, testis, and liver; present in breast milk; FDA Pregnancy Category X

DailyMed; DrugBank

estrogen/ progesterone combinations

68:12 contraceptives IARC Group 1 carcinogen; FDA Pregnancy Category X

DailyMed

estrogens, conjugated

68:16:04 estrogens Black Box warning for endo-metrial cancer and cardio-vascular risks; long-term use in women and laboratory studies increases frequency of several cancers; FDA Preg-nancy Category X

DailyMed

estrogens, esterified

68:16:04 estrogens Black Box warning for endometrial cancer and car-diovascular risks: FDA Preg-nancy Category X

DailyMed

estropipate 68:16:04 estrogens Black Box warning for endo-metrial carcinoma in post-menopausal women and use during pregnancy; FDA Pregnancy Category X

DailyMed; DrugBank

fingolimod 92:20 biologic response modifiers

FDA Pregnancy Category C; in laboratory studies, increased malformations and embryo-fetal deaths at less than the RHD; malignant lymphomas observed in male and female mice.

DailyMed; DrugBank

(continued)

16 17

Table 2 (Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

fluoxymesterone 68:08 androgens Tumors in mice and rats and possibly humans; FDA Preg-nancy Category X

DailyMed; DrugBank

fosphenytoin 28:12.12 hydantoins Metabolized to phenytoin; FDA Pregnancy Category D

DailyMed; DrugBank

ganciclovir 8:18:32 nucleosides and nucleotides

yes FDA Pregnancy Category C DailyMed; DrugBank

leflunomide 92:36 disease-modifying antirheumatic agents

Teratogenic in laboratory studies at 1/10 HD; marked postnatal survival at 1/100 HD; FDA Pregnancy Cate-gory X; severe liver injury reported in patients; carcino-genicity observed at doses below HD

DailyMed; DrugBank

lenalidomide 92:20 biologic response modulators

yes Analog of thalidomide; FDA Black box warnings for limb abnormalaties; pregnancy Cat-egory X; in laboratory studies, caused thalidomide-type limb defects in monkey offspring

DailyMed; DrugBank

liraglutide recombinant

68:20.06 incretin mimetics FDA Pregnancy Category C;Black Box warning for thy-roid C-cell tumors, with supporting evidence in lab-oratory studies; also in labo-ratory studies, teratogenic at or below the MRHD.

DailyMed; DrugBank

medroxyproges-terone acetate

68:32 progestins yes IARC Group 2B; FDA Preg-nancy Category X

DailyMed; DrugBank

(continued)

16 17

Table 2 (Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

mycophenolate mofetil

92:44 immunosuppressive agents

Black Box warning for embryo fetal toxicity, malig-nancies and serious infec-tions; Increased risk of first- trimester pregnancy loss and increased risk of congenital malformations; FDA Preg-nancy Category D; Special warning: tablets should not be crushed and capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in capsules and oral suspension (before or after constitution). If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.

DailyMed; DrugBank

mycophenolic acid

92:44 immunosuppressive agents

Black Box warning for first trimester pregnancy loss and an increased risk of con-genital malformations; FDA Pregnancy Category D; Black Box warning for lymphomas and other malignancies; genotoxic in vitro and in vivo

DailyMed; DrugBank

nevirapine 8:18.08.16 nonnucleoside reverse transcriptase inhibitors

FDA Pregnancy Category B;in laboratory studies, hepa-tocellular adenomas and car-cinomas at doses lower than human dose.

DailyMed; DrugBank

oxcarbazepine 28:12:92 anticonvulsants, miscellaneous

Tumors observed in labora-tory studies at 1/10 MRHD; FDA Pregnancy Category C

DailyMed; Drugbank

(continued)

18 19

Table 2 (Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

palifermin 84:16 cell stimulants and proliferants

FDA Pregnancy Category C; potential for stimulation of tumor growth

DailyMed; Drugbank

phenoxyben-zamine

12:16:04:04 non-selective alpha-andrenergic blocking agents

IARC Group 2B; FDA Preg-nancy Category C

DailyMed; DrugBank

phenytoin 28:12.12 hydantoins IARC 2B; FDA Pregnancy Cat-egory D

DailyMed; DrugBank

pipobroman NA FDA Pregnancy Category D Drugbank

progesterone 68:32 progestins IARC Group 2B DailyMed; Drugbank

progestins 68:12 contraceptives FDA Pregnancy Category X

propylthiouracil 68:36.08 antithyroid agents IARC 2B; FDA Pregnancy Cat-egory D

DailyMed; DrugBank

raloxifene 68:16:12 estrogen ago-nists-antagonists

Abortion and developmental abnormalities seen at low doses in laboratory studies; evidence of tumors at low doses in laboratory studies; FDA Pregnancy Category X

DailyMed; Drugbank

rasagiline 28:36 antiparkinsonian agents

FDA Pregnancy Category C DailyMed; Drugbank

risperidone 28:16:08:04 atypical anti-psychotics

Evidence of tumors at low doses in laboratory studies; may be prolactin-mediated; FDA Pregnancy Category C

DailyMed; DrugBank

sirolimus 92:44 immunosuppressive agents

AKA rapamycin; increased risk of lymphomas and other malignancies; embryotoxic and fetotoxic at 0.2 HD; FDA Pregnancy Category C

DailyMed; DrugBank

(continued)

18 19

Table 2 (Continued). Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug including those with

manufacturers’ safe handling guidance (MSHG)

Drug AHFS classification MSHG Reason for listing Links

spironolactone 24:32.20 mineralocorticoid receptor antagonists

FDA Pregnancy Category C;black box warning for tumorogenicity in laboratory studies.

DailyMed; DrugBank

tacrolimus 92:44 immunosuppressive agents

Increased risk of lymphomas and other malignancies; reproductive effects seen in laboratory studies below the MRHD; excreted in breast milk; FDA Pregnancy Cate-gory C

DailyMed; DrugBank

thalidomide 92:20 biologic response modulators

yes FDA Pregnancy Category X DailyMed; DrugBank

uracil mustard NA yes FDA Pregnancy Category D DrugBank

valganciclovir 8:18:32 nucleosides and nucleotides

yes FDA Pregnancy Category C DailyMed; DrugBank

zidovudine 8:18:08 antiretroviral agents IARC Group 2B; FDA Preg-nancy Category C

DailyMed; DrugBank

20 21

Table 3. Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

acitretin 88:04 vitamin A Black Box warning on adverse reproductive effects; FDA Pregnancy Category X

DailyMed; DrugBank

alitretinoin 84:92 skin and mucous membrane agents, miscel-laneous

FDA Pregnancy Category D DailyMed; DrugBank

ambrisentan 24:12:92 vasodilating agents, miscellaneous

Black Box warning on adverse reproductive effects; reduced sperm counts in patients; FDA Pregnancy Category X

DailyMed;

bosentan 24:12:92 vasodilating agents, miscellaneous

Black Box warning on adverse reproductive effects; FDA Pregnancy Category X

DailyMed; DrugBank

cabergoline 28:36:20:04 ergot-derivative dopamine receptor agonists

Inhibition of conception and embryo fetal effects at doses below recommended human dose; FDA Pregnancy Cate-gory B

DailyMed; DrugBank

cetrorelix 92:40 gonadotropin- releasing hormone anago-nists

FDA Pregnancy Category X DailyMed; DrugBank

choriogonado-tropin

68:18 gonadotropins FDA pregnancy Category C; may cause fetal harm when administered to a pregnant woman.

DailyMed; DrugBank

The drugs in Table 3 primarily meet the NIOSH criteria for reproductive hazards. They represent a potential occupational hazard to males or females who are actively trying to conceive, women who are pregnant or may become pregnant, or breast feeding as they may be present in breast milk. Unopened, intact tablets and capsules may not pose the same degree of occupational risk as injectable drugs that usually require extensive preparation. Cutting, crushing or otherwise manipulating tablets and capsules will increase the risk of expo-sure to workers. Manufacturers’ safe handling guidance (MSHG) is typically in Section 16 of the drug package insert. See Table 5 for safe handling recommendations.*Drugs in red font were added in 2014.

(continued)

20 21

Drug AHFS classification Reason for listing Links

clonazepam 28:12:08 benzodiapines Increased risk of congenital abnormalities when taken in first trimester; FDA Pregnancy Category D

DailyMed; DrugBank

colchicine 92:16 antigout agents FDA Pregnancy Category C; published animal reproduc-tion and development studies indicate it causes embryofetal toxicity, teratogenicity, and altered postnatal develop-ment at exposures within or above the clinical therapeutic range

DailyMed; DrugBank

dinoprostone 76:00 oxytocics Hazardous only for women in late pregnancy; FDA Preg-nancy Category C

DailyMed; DrugBank

dronedarone 24:04:04 antiarrythmics Teratogenic in laboratory studies at ½ MRHD; FDA Preg-nancy Category X

DailyMed; DrugBank

dutasteride 92:08 5-alpha reductase inhibitors

Women warned not to handle; FDA Pregnancy Cate-gory X

DailyMed; DrugBank

ergonovine/meth-ylergonovine

76:00 oxytocics Use is contraindicated during pregnancy because of its uterotonic effects; FDA Preg-nancy Category C

DailyMed; DrugBank; DrugBank

finasteride 92:08 5-alpha reductase inhibitors

Women should not handle crushed or broken finasteride tablets when they are preg-nant or may potentially be pregnant due to potential risk to a male fetus; FDA Preg-nancy Category X

DailyMed; Drugbank

Table 3 (Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

(continued)

22 23

Table 3 (Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

fluconazole 8:18.08 azoles FDA Pregnancy Category C; case reports describe con-genital anomalies in infants exposed in utero to maternal fluconazole (400–800 mg/day) during most or all of the first trimester, similar to those seen in animal studies

DailyMed; DrugBank

ganirelix 92:40 gonadotropin- eleasing hormone antagonists

FDA Pregnancy Category X DailyMed

gonadotropin, chorionic

68:18 gonadotropins Defects of forelimbs and central nervous system and alterations in sex ratio have been reported in laboratory studies; FDA pregnancy Cat-egory C

DailyMed; DrugBank7

icatibant 92:32 complement inhibitors FDA Pregnancy Category C; in laboratory studies, prema-ture birth and abortion rates increased at a dose that was less than 1/40th the MRHD and delayed parturition and fetal death occurred at 0.5 and 2-fold, respectively, the MRHD

DailyMed; DrugBank

mentropins 68:18 gonadotropins FDA Pregnancy Category X Drugbank

methyltestos-terone

68:08 androgens FDA Pregnancy Category X DailyMed; DrugBank

mifepristone 76:00 oxytocics When given to pregnant women results in termination of pregnancy; FDA Pregnancy Category X

DailyMed; DrugBank

misoprostol 56:28.28 prostaglandins FDA Pregnancy Category X DailyMed; DrugBank

(continued)

22 23

Table 3 (Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects

Drug AHFS classification Reason for listing Links

nafarelin 68:18 gonadotropins Note: Given only as nasal spray; no potential for occu-pational exposure; FDA Preg-nancy Category X

DailyMed; DrugBank

oxytocin 76:00 oxytocics Hazardous only for women in 3rd trimester; FDA Pregnancy Category C

DailyMed; DrugBank

paroxetine 28:16:04:20 selective sero-tonin uptake inhibitors

Increased risk of congenital abnormalities when taken in first trimester; complications in pregnancy when taken in third trimester; FDA Preg-nancy Category D

DailyMed; Drugbank

pentetate calcium trisodium

NA Severe teratogenic effects in laboratory studies in dogs: supplied in ampule which can lead to occupational exposure; FDA Pregnancy Category C

DailyMed

plerixafor 20:16 hematopoietic agents Teratogenic in laboratory studies; FDA Pregnancy Cate-gory D

DailyMed; DrugBank

ribavirin 8:18:32 nucleosides and nucleotides

Teratogenic and embryotoxic effects in several laboratory studies; contraindicated in women who are pregnant and in the male partners of women who are pregnant; FDA Pregnancy Category X

DailyMed; DrugBank

telavancin 8:12:28 glycopeptides Black Box warning for poten-tial risk to fetus and adverse reproductive outcomes; reduced fetal weights and increased rates of digit and limb malformations in three species at clinical doses; FDA Pregnancy Category C

DailyMed; Drugbank

(continued)

24 25

Table 3 (Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects*

Drug AHFS classification Reason for listing Links

testosterone 68:08 androgens Children should avoid contact with unwashed or unclothed application sites on skin; FDA Pregnancy Category X

DailyMed; DrugBank

topiramate 28:12.92 anticonvulsants, miscellaneous

FDA Pregnancy Category D DailyMed; DrugBank

tretinoin 84:16 cell stimulants and proliferants

Black Box warning for severe birth defects; Special FDA dis-tribution system; FDA Preg-nancy Category X

DailyMed; DrugBank

ulipristal 68:12 contraceptives FDA Pregnancy Category X DailyMed

valproate/valproic acid

28:12:92 anticonvulsants, miscellaneous

Black Box warning for terato-genicity; congenital malfor-mations including neural tube defects and others; terato-genic in multiple species; FDA Pregnancy Category D

DailyMed; DailyMed; DrugBank

vigabatrin 28:12:92 anticonvulsants, miscellaneous

Malformations seen in labora-tory studies below the MRHD; FDA Pregnancy Category C

DailyMed; Drugbank

voriconazole 8:14.08 azoles FDA Pregnancy Category D DailyMed; DrugBank

warfarin 20:12.04.08 coumarin derivatives

FDA Pregnancy Category D DailyMed; DrugBank

ziprasidone 28:16:08:04 atypical antipsychotics

Developmental toxicity, including possible terato-genic effects at doses similar to human therapeutic doses; an increase in the number of pups born dead and a decrease in postnatal survival at less than MRHD; FDA Preg-nancy Category C

DailyMed; Drugbank

(continued)

24 25

Table 3 (Continued). Non-antineoplastic drugs that primarily have adverse reproductive effects*

Drug AHFS classification Reason for listing Links

zoledronic acid 92:24 bone resorption inhibitors

Number of stillbirths increased and survival of neo-nates decreased in laboratory studies at low doses; FDA Pregnancy Category D

DailyMed; DrugBank

zonisamide 28:12:92 anticonvulsants, miscellaneous

Teratogenic in multiple animal species; FDA Preg-nancy Category C

DailyMed; DrugBank

26 27

Table 4a. Drugs deleted from the 2004 hazardous drug list for not meeting the NIOSH criteria for hazardous drugs

Drug AHFS Classification*

aldesleukin 10:00 antineoplastic agents

asparaginase 10:00 antineoplastic agents

denileukin 10:00 antineoplastic agents

estrone 68:16.04 estrogens

nilutamide 10:00 antineoplastic agents

pegaspargase 10:00 antineoplastic agents

pentamidine isethionate 8:40 miscellaneous anti-infectives

podofilox/podophyllum resin 84:36 miscellaneous skin and mucous membrane agents (mitotic inhibitor)

testolactone 10:00 antineoplastic agents

trifluridine 52:04.06 antivirals

vidarabine 52:04.06 antivirals

Table 4 lists drugs that were deleted from the 2004 and 2012 NIOSH hazardous drug lists. The 2004 list was a composite of five separate lists. When the drugs on that list were reviewed against the NIOSH criteria for hazardous drugs, these 11 drugs did not meet the criteria. Tetracycline was removed from the 2012 list on the basis of feedback from stakeholders.*AHFS = American Hospital Formulary Service.

Table 4b. Drugs deleted from the 2012 list on the basis of stakeholder comments

Drug AHFS Classification*

Tetracycline 8:12.24 tetracyclines

26 27

Table 5 provides general guidance for some of the possible scenarios that may be encountered in health care settings where hazardous drugs are handled, but it cannot cover all possible situations. This guidance applies to the drugs in Tables 1–3. For more detailed information on safe-handling practices, see the reference list [NIOSH 2004; ASHP 2006; USP 2008; ONS 2011].

Table 5. Personal protective equipment and engineering controls for working with hazardous drugs in healthcare settings*

Formulation ActivityDouble gloves

Protective gown

Eye protection

Respiratory protection

Ventilated engineering

controls

Intact tablet or capsule

Administration from unit-dose package

no (single glove should be used)

no no no N/A

Tablets or cap-sules

Cutting, crushing or otherwise manipulating tablets or cap-sules

yes yes no yes, if not done in a control device

yes†

Administration yes yes no2 yes, if powder generated

N/A

Oral liquid drug

Compounding yes yes yes, if not done in a control device

yes, if not done in a control device

yes†

Administration yes yes no‡ no‡ N/A

Topical drug Compounding yes yes yes yes, if not done in a control device

yes†

Administration yes yes yes, if liquid that could splash‡

yes, if inhalation potential

N/A

Ampoule Opening yes yes yes, if not done in a control device

yes, if not done in a control device

yes, BSC or CACI

(continued)

28 29

Table 5 (Continued). Personal protective equipment and engineering controls for working with hazardous drugs in healthcare settings*

Formulation ActivityDouble gloves

Protective gown

Eye protection

Respiratory protection

Ventilated engineering

controls

Subcutaneous, intramuscular injection

Preparation (withdrawing from vial or ampoule)

yes yes yes, if not done in a control device

yes, if not done in a control device

yes, BSC or CACI

Administration from prepared syringe

yes yes yes, if liquid that could splash‡

yes, if inhalation potential‡

N/A

Intravenous solution

Compounding yes yes yes, if not done in a control device

yes, if not done in a control device

yes, BSC or CACI; recom-mend use of CSTD

Administration of prepared solution§

yes yes yes, if liquid that could splash‡

yes, if inhalation potential‡

N/A; recom-mend use of CSTD

Solution for irrigation

Compounding yes yes yes, if not done in a control device

yes, if not done in a control device

yes, BSC or CACI; recom-mend use of CSTD

Administration (bladder, HIPEC, limb perfusion, etc.)

yes yes yes yes N/A

Powder/ solution for inhalation

Inhalation yes yes yes yes yes, when applicable

*The table provides general guidance for some of the possible scenarios that may be encountered in healthcare settings, but cannot cover all possible situations. For more detailed information on safe handling practices, see the reference list [NIOSH 2004; ASHP 2006; USP 2008, and ONS 2011]. BSC = Class II biological safety cabinet; CACI = compounding aseptic containment isolator; CSTD = closed system drug transfer device; HIPEC = hyper-thermic intraperitoneal chemotherapy.

†For nonsterile preparations, an engineering control such as a fume hood or Class I BSC is sufficient. It is recommended that these activities be carried out in a control device, but it is recognized that under some circumstances, it is not possible. If the activity is performed in an engineering control that is used for sterile intravenous preparations, a thorough cleaning is required following the activity.

‡Required if patient may resist (infant, unruly patient, veterinary patient) or if administered by feeding tube.§Intravenous tubing already attached and primed.

28 29

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DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150)

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